What is Refractory Hypoxemia and Venovenous ECMO?
Refractory hypoxemia is a condition that can occur in a small group of patients with severe breathing problems and who require a ventilator for support. This condition, where a person’s oxygen levels remain dangerously low even after attempts to increase it, is mostly seen in individuals suffering from a condition called Acute Respiratory Distress Syndrome (ARDS) – a severe form of lung inflammation. It’s worth noting that refractory hypoxemia can be quite challenging for doctors in the intensive care unit because most treatment strategies can only increase oxygen levels without necessarily improving the patient’s survival chances.
There’s no universally accepted definition of refractory hypoxemia; it’s generally considered to be the case when the oxygen levels in a person’s arterial blood remain low despite receiving substantial amounts of supplemental oxygen. There are varying opinions among different intensive care specialists as to what exactly constitutes refractory hypoxemia.
Some of the definitions found in medical literature involve specific measurements of oxygen. For example, when the partial pressure of oxygen (PaO2 – a measurement of oxygen pressure in arterial blood) remains less than or equal to 60 mmHg, or when the ratio between PaO2 and FiO2 (fraction of inspired oxygen – the concentration of oxygen that a person inhales) drops to 100 or lower. These conditions need to persist for over 12 hours, at high pressure settings on the ventilator and despite adopting lung-protective strategies with lower volumes of air given with each breath.
There’s an additional measurement tool called the Oxygenation Index (OI) which is useful in evaluating refractory hypoxemia. This formula combines airway pressure and the oxygen measurements (PaO2/FiO2). An OI result of less than 40 indicates persistent low oxygen levels despite using conventional ventilation methods and therefore, may require further advanced therapies.
When all other strategies fail to improve oxygen levels, including adjusting the ventilator settings, position changes, muscle relaxants to improve coordination with the ventilator, and medications to relax blood vessels in the lungs, a more aggressive approach with a machine – called extracorporeal membrane oxygenation (ECMO), might be required to take over the work of the lungs to oxygenate the blood.
What Causes Refractory Hypoxemia and Venovenous ECMO?
Refractory hypoxemia is a medical condition where there’s not enough oxygen in the blood, and it doesn’t improve with oxygen treatment. It can occur due to many reasons including severe infections (sepsis), pneumonia, serious injuries, inhaling water (as in drowning), burns, smoke inhalation, receiving a lot of blood transfusions, blockage of blood vessels caused by air, fat, or amniotic fluid (which surrounds a baby in the womb), poisonings, and radiation exposure.
The most common cause of this stubbornly low oxygen level in the blood is a severe lung injury from a disease called Acute Respiratory Distress Syndrome or ARDS. ARDS is a condition where the lungs become very inflamed and filled with fluid, making it hard to breathe and get enough oxygen into the bloodstream.
Risk Factors and Frequency for Refractory Hypoxemia and Venovenous ECMO
Severe low oxygen levels in the blood, known as severe hypoxemia, can impact 20% to 30% of people with ARDS (Acute Respiratory Distress Syndrome). This condition is linked to a higher death rate. It’s estimated that 10% to 15% of ARDS-related fatalities are directly caused by this unmanageable low oxygen level.
Signs and Symptoms of Refractory Hypoxemia and Venovenous ECMO
ARDS, or Acute Respiratory Distress Syndrome, mainly causes shortness of breath which gradually gets worse, often needing support from a breathing machine. A careful medical history and physical examination can usually help identify the cause. Symptoms that might be found during a check-up include rapid breathing, lower than normal levels of oxygen in the blood, fast heart rate, and bluish skin color. Listening to the lungs may reveal unusual crackling sounds, particularly at the base of the lungs, and signs of reduced airflow in severe situations.
To ensure the symptoms are not due to heart failure, which can show similar signs, it would be necessary to check for specific heart-related symptoms. This could include listening for certain heart sounds, checking for neck vein swelling, an enlarged liver, swelling in the ankles or fluid in the abdomen.
It’s important to assess the patient’s neurological and blood flow status to understand the effects of low oxygen levels on body organ function. Changes in mental activity, feeling confused, having cold limbs, and decreased amounts of urine can all indicate conditions of shock due to low oxygen levels or the underlying cause of low oxygen levels in the blood.
- Shortness of breath
- Rapid breathing
- Low oxygen levels in the blood
- Fast heart rate
- Bluish skin color
- Crackling sounds in lungs
- Reduced airflow in severe situations
- S-specific heart-related symptoms to rule out heart failure
- Changes in mental activity
- Feeling confused
- Cold limbs
- Decreased amounts of urine
Testing for Refractory Hypoxemia and Venovenous ECMO
To check for conditions like lung infiltrations (accumulated fluid or particles in the lungs) or ARDS (a serious lung condition called Acute Respiratory Distress Syndrome), or if the pneumonia started in the lungs, your doctor might take an X-ray of your chest. They may also carry out a test called an arterial blood gas test to monitor the amount of oxygen in your bloodstream, in order to assess the severity of a condition known as hypoxemia, which is low oxygen levels in the blood.
Additionally, computed tomography (commonly known as a CT scan) of your chest might be more reliable and precise than a chest X-ray in spotting complications from ARDS.
If needed, your doctor might perform a test called a transthoracic echocardiogram: a type of ultrasound used to image the heart. This can help rule out heart-related causes of hypoxemia, such as intracardiac shunting (where blood bypasses the lungs), congestive heart failure resulting in fluid build-up in the lungs or high blood pressure in the lungs leading to strain on the right side of the heart (known as cor pulmonale). In cases of severe double lung blood clots causing resistant hypoxemia, conducting an echocardiogram might show a strain on the right chamber of your heart.
Treatment Options for Refractory Hypoxemia and Venovenous ECMO
It’s crucial to remember that ensuring the essential functions of organs by delivering adequate oxygen is more important than fixing severely low levels of oxygen in the blood. To improve this condition, doctors might use a technique called lung recruitment. It helps open up the lungs and uses the remaining healthy parts of the lungs to improve the exchange of air, which can increase the oxygen available for the body.
Lung recruitment can be achieved through various strategies, usually involving applying pressure to the lungs via a ventilator, but it’s still unknown how often these procedures should be done. While these strategies can help improve oxygen levels, they may also put pressure on healthy lung areas, sometimes causing low blood pressure and low oxygen levels. Sometimes, these lung recruitment attempts might be used as a temporary solution while waiting for a more effective treatment for life-threatening low oxygen levels.
There are different modes of ventilation (method of air delivery via machines) suggested, but no single method has been proven to be superior. If low oxygen levels persist despite all these measures, doctors might consider additional treatments. These might include positioning the patient face-down (prone), use of drugs that dilate lung blood vessels, drugs to prevent patient-ventilator mismatch, limited fluid intake, corticosteroid medications, and use of a machine that does the job of the lungs (extracorporeal membrane oxygenation, or ECMO). There’s not enough research to compare which of these treatments work best.
Neuromuscular blocking agents (NMBAs) are types of medications that can help improve patient-ventilator compatibility by reducing the work the lungs have to do, leading to more evenly distributed lung use and improved oxygen supply. They should be considered for patients with severe low oxygen levels due to moderate-severe Acute Respiratory Distress Syndrome (ARDS). They should be used with caution, however, particularly in patients on steroids, and ideally for less than 48 hours due to the risk of muscle disease.
Positioning the patient face-down can alleviate the pressure of the heart on the lungs and helps distribute air more evenly in the lungs, thus improving the oxygen supply. However, this can cause complications. For example, it could lead to facial swelling, increased need for sedation medication, and the risk of accidentally removing breathing or intravenous tubes. This is why this solution might not be a feasible option for everyone and should be performed by an experienced team.
There’s still debate over whether using both patient face-down positioning and neuromuscular blocking agents together could collectively enhance oxygenation.
ECMO is an advanced life-support method that can be used for patients who have severe low oxygen levels and have not responded to other therapies. ECMO works similarly to the heart-lung bypass used in open-heart surgery. It essentially does the job of the lungs and sometimes the heart by extracting, oxygenating, and returning the patient’s own blood.
ECMO can be done through two methods: venovenous (VV) for patients with severe lung failure but good heart function, and venoarterial (VA) for those with severe lung and heart failure. During VV ECMO, blood is removed from a major vein, oxygenated, and then returned to the body via another major vein. Before this procedure, the patient will be given medication to prevent blood clotting.
This therapy allows the doctors to maintain limited ventilator settings while ensuring the patient is adequately oxygenated. It can sometimes run for several weeks. Studies have found that the mortality rate in patients with severe low oxygen levels treated with ECMO was lower compared to those treated conventionally.
However, if the low oxygen levels persist even after initiating ECMO, other strategies can be considered. These include increasing the ECMO blood flow, improving the oxygen-carrying capacity, and reducing the oxygen consumption by inducing a state of unconsciousness, complete muscle relaxation, and therapeutic cooling. Lastly, there’s a known concern about recirculation, which is when oxygenated blood accidentally gets drawn back into the ECMO machine instead of going through pulmonary circulation.
The process to wean off ECMO can begin when there’s improvement seen on the chest X-ray, lung flexibility, and blood oxygen concentration. Some patients often trial periods off ECMO by removing all the gases from the machine but keeping a constant blood flow. This is done for several hours while adjusting the patient’s ventilator settings to ensure suitable oxygenation and ventilation. It’s important to note that not everyone is a candidate for ECMO, especially those with conditions incompatible with recovery such as end-stage cancer or severe neurological injury.
What else can Refractory Hypoxemia and Venovenous ECMO be?
While the conditions that lead to ARDS (acute respiratory distress syndrome) are typically the main causes behind persistent low oxygen levels in the blood, there are other conditions that need to be considered.
- Heart-related conditions, such as atrial septal defect or patent foramen ovale, which can cause significant unusual blood flow from the right to left chambers of the heart
- Intrapulmonary shunts, which are conditions that could lead abnormal blood flow in the lungs like pulmonary arteriovenous malformations and hepatopulmonary syndrome
- Acute pulmonary embolism (blood clot in the lungs) and pulmonary hypertension (high blood pressure in the arteries to your lungs) which are dangerous and could be life-threatening.
These possible causes need to be considered and ruled out in cases of persistent low blood oxygen levels.
What to expect with Refractory Hypoxemia and Venovenous ECMO
The risk of death is notably high for patients suffering from stubborn, or refractory, low oxygen levels in the blood, often referred to as hypoxemia. Generally, patients with severe hypoxemia have about a 90% chance of death, even after all other treatments have been attempted, apart from ECMO (Extracorporeal Membrane Oxygenation).
ECMO, acting like an artificial lung, can raise the chances of survival to between 40% and 93%, depending on the specific condition of the patient. The CESAR trial, a medical study, compared standard ventilation therapy against ECMO in patients with severe hypoxemia. The results showed that the patients who received ECMO had a significantly higher survival rate of 63%, whereas those who received conventional therapy had a rate of 47%.
Possible Complications When Diagnosed with Refractory Hypoxemia and Venovenous ECMO
The main problems associated with ECMO, a technique to aid breathing and heart function, are bleeding and blood clot formation, which can block blood vessels. About 30-50% of patients on ECMO experience bleeding. To reduce the chances of bleeding, it’s important to keep the number of platelets (a type of blood cell that helps with clotting) above 50000/mL and to monitor clotting time.
To manage bleeding, medical providers can use drugs that stop the breakdown of blood clots, such as aminocaproic acid, or pause the use of heparin (a medication that prevents clotting) for several hours. However, these measures can increase the risk of blood clot formation in the ECMO system.
The presence of a blood clot within the ECMO system can lead to systemic thromboembolism, a very serious condition where clots block blood flow to important organs. To prevent this, it’s crucial to regularly check all components of the system and monitor changes in the pressure gradient (the difference in pressure between two points) across the oxygenator, which adds oxygen to the blood. A sudden change could mean a clot has formed.
Additional risks include the puncture or rupture of a blood vessel, leading to heavy bleeding, and damage to the walls of an artery during the insertion of the ECMO tubes.
Common Risks of ECMO:
- Bleeding (experienced by 30-50% of patients)
- Blood clot formation within the ECMO system
- Increased risk of clotting when adjusting medication to control bleeding
- Possible puncture or tearing of blood vessels during ECMO tube insertion
Preventing Refractory Hypoxemia and Venovenous ECMO
It’s crucial to use methods to prevent ARDS, a condition that often leads to severe, persistent low oxygen levels in the blood. This disease is usually seen in patients who have had sepsis (a dangerous infection that can affect the whole body) or pneumonia (a lung infection). So it’s important to identify those who are at a high risk of developing a lung injury early on.
Following certain preventive measures can help keep the lungs safe, such as following a type of care known as lung-protective ventilation – this is a way to help the patient breathe while lessening the chance of further lung damage. Other measures might include being cautious with blood transfusions, using steps to prevent aspiration (accidentally breathing in food or liquid), and properly managing sepsis or septic shock (a serious condition caused by sepsis), as well as injuries from trauma.
